Enzymatic carboxymethylation of proteins is a post-translational modification. By changing the structure and properties of membrane proteins, carboxymethylation provides an important regulatory mechanism. Receptors being the molecules that receive signals from the exterior of the cell and transmit information to its interior are thus obvious targets for regulating modification. The purified acetylcholine receptor (AcChoR) is a complex of five polypeptides and is an excellent substrate for the enzyme protein carboxyl methylase (PCM). AcChoR enriched membranes are also excellent substrates for PCM. These membranes are closed right-side out vesicles. By the use of freeze-thaw techniques, PCM can be introduced into the vesicles and methylate them from the inside. Separation of the methylated pure AcChoR, and inside methylated vesicles on gel electrophoresis shows that all of the receptor subunits are methylated. The 60K polypeptide has the highest specific activity, while the 40K the lowest. Thus the data shows both specificity of the receptor subunits.